The pharmaceutical industry is a multi-billion dollar international commercial field. Like many industries however, many of the products of the pharmaceutical industry fall prey to counterfeiters who manufacture substandard or fake imitation products, and sell them for a fraction of their real market price. Worldwide, the percentage of drugs that are counterfeit has become high enough to seriously impact the revenue of major pharmaceutical companies. Even more serious is the potential health risks involved for the consumer of counterfeit drugs.
Besides the infringement of intellectual property rights as well as the breaking of other governmental laws, the Federal Drug Administration (FDA) does not yet have an all encompassing solution to the pharmaceutical industry's counterfeit problem.
There have been several attempts by the prior art to overcome the problem of counterfeit drugs, however, each of the prior art solutions has drawbacks associated with it. Some prior art technologies utilize RFID and bar coding to read the package labels to determine the authenticity of the contents contained therein. This, however, does not necessarily provide accurate results since the product itself is not directly analyzed.
The prior art has also developed drug authenticating procedures based on the concept of the spectral signature. Every drug has a unique spectral signature (or, fingerprint) determined by its molecular composition. Infrared (IR) spectroscopy is used to determine whether the molecular composition of the sample product is identical to known spectral signature of the authentic product. IR spectroscopy is the subset of spectroscopy that deals with the Infrared region of the electromagnetic spectrum. Infrared spectroscopy exploits the fact that molecules have specific frequencies at which they rotate or vibrate in relation to discrete energy levels.
U.S. Pat. No. 6,395,538 deals with the fields of bio-manufacturing and infrared spectroscopy, particularly, quality monitoring and control of a biomaterial, for instance in a biologically active pharmaceutical ingredient. Fourier transform infrared spectroscopy is used to monitor the production of a biomolecule and to fingerprint, both qualitatively and quantitatively, the biomolecule at different stages of a biomanufacturing process. U.S. Pat. No. 6,395,538, which as said relates to a spectroscopy based system, is also not concerned with counterfeit drugs on the commercial level, and therefore the system is not concerned with overcoming difficulties such as determining the authenticity of a plurality of pharmaceutical products contained within a sealed package.
U.S. Pat. No. 6,853,447 pertains to the screening and identification of materials such as pharmaceutical or food products being packaged in an automated machine. The invention utilizes an array of imaging spectrometers. The system of U.S. Pat. No. 6,853,447 performs spectroscopy in the near IR and short IR spectra. In contrast to thermography which detects the level of the IR emission from an object and the distribution of the IR emission from the object, spectroscopy checks LR reflection from the product, or more particularly, the spectral distribution of the reflection in the frequency domain The determination of the spectra of U.S. Pat. No. 6,853,447 allows only inspection of the external surface of a product, and cannot relate to the body of the product. Therefore, when applying the spectroscopy of U.S. Pat. No. 6,853,447, each drug has to be inspected individually, outside of its container. This makes it problematic to operate when the pharmaceutical product is in a liquid state. Additionally, many capsules are coated by a thin layer of, for instance, gelatin, which blocks the near IR detector device from determining the authenticity of the drug. Moreover, utilizing such a method on a commercial scale is costly due to the amount of time required for each inspection.
U.S. Pat. No. 6,771,369 relates to the validation and identification of packaged pharmaceuticals in a retail setting. A chemical analysis and validation system preferably utilizes visual (Vis) and near infrared (NIR) spectroscopy to analyze and identify the contents of the filled prescription vial by measuring the chemical signature of the items. Other variations can also be used, for example, various forms of optical spectroscopy, UV-Vis, UV-Vis-NIR, infrared or Raman spectroscopy. The system of U.S. Pat. No. 6,771,369, similar to that of U.S. Pat. No. 6,853,447, produced by the same company, performs detection only in the near and shortwave IR spectra. As described above, operation in these spectra only allow detection of the external surface of a product, therefore, each drug must be inspected individually, outside of the container. On a commercial scale, such a limitation is a severe hindrance to the efficiency of counterfeit checking. Moreover, it is problematic to check a pharmaceutical product in the liquid state. Additionally, as described herein above, many capsules are coated by a thin layer of, for instance, gelatin, which blocks the detector device from determining the authenticity of the drug.
U.S. Pat. No. 7,126,685 describes an optical absorption spectroscopy method comprising providing a container such as a pharmaceutical bottle containing a sample, rotating the container, directing a beam comprising one or more wavelengths consisting of visible wavelengths, infrared wavelengths and ultraviolet wavelengths, and measuring characteristics of the beam after it passes through the container. U.S. Pat. No. 7,126,685 does not deal with detection of counterfeit drugs, let alone on a commercial scale, and therefore does not provide solutions to the above-mentioned counterfeit problems of the industry.
In the prior art, the development of IR technology for the detection of counterfeit drugs has been entirely limited to the field of spectroscopy, particularly near IR. Near IR spectroscopy is restricted in its detection capabilities since it is limited to surface (e.g. drug coating, outer packaging, etc.) reflection. In spectroscopy, the molecular structure of a pharmaceutical product is measured in the frequency domain, and the distinctive curvature is analyzed with corresponding signatures to determine the authenticity of the drug.
Thermography is a type of infrared imaging in which radiation emitted from objects is detected based on the temperature at different locations across the body, and images are produced of that radiation. In passive thermography an image of the emitted radiation is acquired of an object at a steady state temperature. In active thermography, a thermal pulse is applied to the object to change its temperature, and multiple images are acquired during the entire temperature cycle from the moment that the temperature heat pulse is applied until the sample pharmaceutical product reaches the ambient temperature, and over a predetermined time period.
Thermography measures the distribution of the emission from an object, and it operates only in the mid-wavelength IR (MWIR between 3-5.4 micrometers), and the long-wavelength IR (LWIR between 8-14 micrometers). This is in contrast to spectroscopy which relates to the spectral distribution of the reflection from the object mostly in the NIR (near IR) and SWIR (Short Wave IR). It has been found by the inventors that the use of thermography allows inspection deep into the object, i.e., well beyond the surrounding container and the external surface of the object.
While thermal based systems, particularly in the field of thermography, are well exploited in areas such as military/security systems, non destructive testing, and medical imaging, such systems have never been suggested for detecting counterfeit of products, particularly in the pharmaceutical industry.
It is therefore an object of the present invention to provide method and system for determining the authenticity of a pharmaceutical product that overcome the drawbacks associated with the prior art.
It is another object of the present invention to provide method and system for determining the authenticity of a pharmaceutical product by means of thermography, i.e., by means of an IR imaging system which operates in the MWIR or LWIR spectrum.
It is an additional object of the present invention to provide method and system for determining the authenticity of a pharmaceutical product by means of passive or active thermography.
It is still another object of the present invention to provide method and system that can inspect deep into a pharmaceutical product and determine counterfeit.
It is still another object of the present invention to provide method and system that can inspect and determine counterfeit of a pharmaceutical product, even from outside of the product package, and which does not require opening of the package.
It is still another object of the present invention to provide method and system that can inspect and determine counterfeit of plurality of pharmaceutical products that are packaged together, without need for opening the package.
It is still another object of the present invention to provide method and system that can inspect and determine counterfeit of pharmaceutical products from the outside of a multi-layer package.
It is still another object of the present invention to provide method and system that can inspect and determine counterfeit of a liquid pharmaceutical product from the outside of its container.
It is still another object of the present invention to provide method and system that enable a manufacturer of pharmaceutical product to design a hard to counterfeit unique signature for the product, and which can be easily verified.
Additional objects and advantages of the present invention will become apparent as the description proceeds.